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  1. Article ; Online: A single mutation in the E2 glycoprotein of hepatitis C virus broadens the claudin specificity for its infection

    Yoshitaka Shirasago / Hidesuke Fukazawa / Shotaro Nagase / Yoshimi Shimizu / Tomoharu Mizukami / Takaji Wakita / Tetsuro Suzuki / Hideki Tani / Masuo Kondoh / Takuya Kuroda / Satoshi Yasuda / Yoji Sato / Kentaro Hanada / Masayoshi Fukasawa

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 12

    Abstract: Abstract Entry of the hepatitis C virus (HCV) into host cells is a multistep process mediated by several host factors, including a tight junction protein claudin-1 (CLDN1). We repeatedly passaged HCV-JFH1-tau, an HCV substrain with higher infectivity, on ...

    Abstract Abstract Entry of the hepatitis C virus (HCV) into host cells is a multistep process mediated by several host factors, including a tight junction protein claudin-1 (CLDN1). We repeatedly passaged HCV-JFH1-tau, an HCV substrain with higher infectivity, on Huh7.5.1-8 cells. A multi-passaged HCV-JFH1-tau lot was infectious to CLDN1-defective S7-A cells, non-permissive to original HCV-JFH1-tau infection. We identified a single mutation, M706L, in the E2 glycoprotein of the HCV-JFH1-tau lot as an essential mutation for infectivity to S7-A cells. The pseudovirus JFH1/M706L mutant could not infect human embryonic kidney 293 T (HEK293T) cells lacking CLDN family but infected HEK293T cells expressing CLDN1, CLDN6, or CLDN9. Thus, this mutant virus could utilize CLDN1, and other CLDN6 and CLDN9, making HCV possible to infect cells other than hepatocytes. iPS cells, one of the stem cells, do not express CLDN1 but express CLDN6 and other host factors required for HCV infection. We confirmed that the HCV-JFH1-tau-derived mutant with an M706L mutation infected iPS cells in a CLDN6-dependent manner. These results demonstrated that a missense mutation in E2 could broaden the CLDN member specificity for HCV infection. HCV may change its receptor requirement through a single amino acid mutation and infect non-hepatic cells.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Direct Inhibition of SARS-CoV-2 Spike Protein by Peracetic Acid

    Yuichiro Yamamoto / Yoshio Nakano / Mana Murae / Yoshimi Shimizu / Shota Sakai / Motohiko Ogawa / Tomoharu Mizukami / Tetsuya Inoue / Taishi Onodera / Yoshimasa Takahashi / Takaji Wakita / Masayoshi Fukasawa / Satoru Miyazaki / Kohji Noguchi

    International Journal of Molecular Sciences, Vol 24, Iss 1, p

    2022  Volume 20

    Abstract: Peracetic acid (PAA) disinfectants are effective against a wide range of pathogenic microorganisms, including bacteria, fungi, and viruses. Several studies have shown the efficacy of PAA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...

    Abstract Peracetic acid (PAA) disinfectants are effective against a wide range of pathogenic microorganisms, including bacteria, fungi, and viruses. Several studies have shown the efficacy of PAA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, its efficacy in SARS-CoV-2 variants and the molecular mechanism of action of PAA against SARS-CoV-2 have not been investigated. SARS-CoV-2 infection depends on the recognition and binding of the cell receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD) of the spike protein. Here, we demonstrated that PAA effectively suppressed pseudotyped virus infection in the Wuhan type and variants, including Delta and Omicron. Similarly, PAA reduced the authentic viral load of SARS-CoV-2. Computational analysis suggested that the hydroxyl radicals produced by PAA cleave the disulfide bridges in the RBD. Additionally, the PAA treatment decreased the abundance of the Wuhan- and variant-type spike proteins. Enzyme-linked immunosorbent assay showed direct inhibition of RBD-ACE2 interactions by PAA. In conclusion, the PAA treatment suppressed SARS-CoV-2 infection, which was dependent on the inhibition of the interaction between the spike RBD and ACE2 by inducing spike protein destabilization. Our findings provide evidence of a potent disinfection strategy against SARS-CoV-2.
    Keywords SARS-CoV-2 ; peracetic acid ; spike protein ; receptor-binding domain ; ACE2 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 612
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: The Role of Hypertriglyceridemia in the Development of Atherosclerosis and Endothelial Dysfunction

    Saki Matsumoto / Nozomi Gotoh / Saori Hishinuma / Yohei Abe / Yoshimi Shimizu / Yumi Katano / Akira Ishihata

    Nutrients, Vol 6, Iss 3, Pp 1236-

    2014  Volume 1250

    Abstract: A hereditary postprandial hypertriglyceridemic rabbit (PHT rabbit) is a new dyslipidemic model showing remarkably high plasma triglycerides with only limited elevation of plasma total cholesterol. In PHT rabbits, plasma triglyceride was markedly elevated ...

    Abstract A hereditary postprandial hypertriglyceridemic rabbit (PHT rabbit) is a new dyslipidemic model showing remarkably high plasma triglycerides with only limited elevation of plasma total cholesterol. In PHT rabbits, plasma triglyceride was markedly elevated postprandially compared with healthy Japanese white (JW) rabbits. In physiological experiments, the ring preparation of the thoracic aorta was suspended in an organ bath filled with modified Krebs-Henseleit solution, and the developed tension was recorded. Endothelial function was evaluated by acetylcholine-induced vasorelaxation in each preparation with intact endothelium. The acetylcholine-induced endothelium-dependent relaxation was diminished in PHT compared with JW rabbits, suggesting endothelial dysfunction in PHT rabbits. Histological examination was carried out in adipose tissue, liver and aorta. They were fixed in formaldehyde and embedded in paraffin. The tissues were sliced (4 μm) and stained using hematoxylin-eosin solution. In the adipose tissue, the visceral fat accumulated, and the size of adipose cells was enlarged in PHT rabbits. The liver of the PHT rabbit was fatty and degenerated. In aorta, increased intimal thickness was observed, suggesting the progression of atherosclerosis in the PHT rabbit. This study suggests the important role of postprandial hypertriglyceridemia in atherosclerosis. By using PHT rabbits, the effects of hypertriglyceridemia on health and diseases could be evaluated precisely.
    Keywords hypertriglyceridemia ; atherosclerosis ; visceral fat ; liver ; aorta ; endothelium ; Nutrition. Foods and food supply ; TX341-641 ; Home economics ; TX1-1110 ; Technology ; T ; DOAJ:Nutrition and Food Sciences ; DOAJ:Agriculture and Food Sciences
    Subject code 630
    Language English
    Publishing date 2014-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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